Congestive heart failure is a disease in which cardiac output deteriorates because of the malfunction of the heart, outputting only insufficient blood supply for the metabolism of tissue. Recently, J. N. Cohn has described the congestive heart failure as a syndrome caused by failure of the function of the heart which is accompanied by (1) deterioration of motor tolerance capacity, (2) multiple ventricular arrhythmia, and (3) signs indicating unfavorable symptoms (J. N. Cohn: Circulation 78, 1099 (1988)).
To ameliorate the above symptom-complex, diuretic agents, vasodilators, and cardiac tonics such as digitalis have conventionally been employed.
These days, digitalis agents are the most common cardiac tonics. Digoxin, one of the digitalis components, is known to promote the ejection of the heart, thereby preventing the cardiac insufficiency from aggravated. Digoxin has also remarkable advantages in that it lowers the cardiac rate, its effects last long, it does not have drug resistance, and it can be orally dosed. On the other hand, since the effective blood level of digoxin is close to its toxic level, it sometimes induces arrhythmia. Therefore, oral preparations of non-glycoside cardiac tonics have become of interest and, active studies are being made recently.
Accordingly, an object of the present invention is to provide a compound useful for the treatment of heart diseases which is free from the above mentioned drawbacks, and which has positive inotropic action, antiarrhythmic action and vasodilating action.
Under the above mentioned circumstances, the inventors of the present invention have synthesized many compounds, and have carried out screening of the compounds in view of the positive inotropic action, antiarrhythmic action and vasodilating action, and as a result, have found that the novel quinoline derivatives represented by the following formula (1) or their medicinally acceptable salts are suited for the above-mentioned purposes and are useful as medicines for the treatment of heart diseases, leading to completion of the invention.